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X-linked Spondyloepiphyseal Dysplasia Tarda with Mutation in TRAPPC2Gene: First Report from India.

ABSTRACT: Introduction:X-linked spondyloepiphyseal dysplasia tarda(SEDT) is a type of shorttrunk skeletal dysplasia, occurring in males due to mutation in TRAPPC2 gene. Case Report:We describe a large Indian family with multiple males affected with X-linked SEDT. The affected individuals presented with disproportionate short stature, short trunk, and barrel-shaped chest. Elder sibs aged 26 years and 31 years had back and hip pain. Premature osteoarthritis was seen requiring hip replacement surgery in one sib. The known pathogenic nonsense mutation c.209G>A (p.W70X) was identified in TRAPPC2 gene. This is the first mutation proven Indian kindred with X-linked SEDT. Conclusion:Knowledge of molecular basis is essential to provide definitive diagnosis, accurate counseling, and prenatal diagnosis or early postnatal diagnosis for this rare condition.

SUBMITTER: Tamhankar PM

PROVIDER: S-EPMC7476708 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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X-linked Spondyloepiphyseal Dysplasia Tarda with Mutation in TRAPPC2Gene: First Report from India.

Tamhankar Parag M PM Kulkarni Abhishek A Vasudevan Lakshmi L

Journal of orthopaedic case reports 20200101 2

<h4>Introduction</h4>X-linked spondyloepiphyseal dysplasia tarda(SEDT) is a type of shorttrunk skeletal dysplasia, occurring in males due to mutation in TRAPPC2 gene.<h4>Case report</h4>We describe a large Indian family with multiple males affected with X-linked SEDT. The affected individuals presented with disproportionate short stature, short trunk, and barrel-shaped chest. Elder sibs aged 26 years and 31 years had back and hip pain. Premature osteoarthritis was seen requiring hip replacement ...[more]

PMID: 32953644

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Project description:BACKGROUND:Spondyloepiphyseal dysplasia tarda (SEDT) is a rare X-linked recessive inherited osteochondrodysplasia caused by mutations in the TRAPPC2 gene. It is clinically characterized by disproportionate short stature and early onset of degenerative osteoarthritis. Clinical diagnosis can be challenging due to the late-onset of the disease and lack of systemic metabolic abnomalites. Genetic diagnosis is critical in both early diagnosis and management of the disease. Here we reported a five-generation Chinese SEDT family and described the novel molecular findings. METHODS:Detailed family history and clinical data were collected. Genomic DNA was extracted from venous blood samples of family members. The exons of genes known to be associated with skeletal disorders were captured and deep sequenced. Variants were annotated by ANNOVAR and associated with multiple databases. Putative variants were confirmed by Sanger sequencing. The identified variant was classified according to the American College of Medical Genetics (ACMG) criteria. RESULTS:The proband was a 27-year-old Chinese male who presented with short-trunk short stature and joint pain. His radiographs showed platyspondyly with posterior humping, narrow hip-joint surfaces, and pelvic osteosclerosis. A pedigree analysis of 5 generations with 6 affected males revealed an X-linked recessive mode of inheritance. Affected males were diagnosed as SEDT according to the clinical and radiological features. Next-generation sequencing identified a novel variant of c.216_217del in the exon 4 of TRAPPC2 gene in the proband and other affected males. This variant resulted in the shift of reading frame and early termination of protein translation (p.S73Gfs*15). The mother and maternal female relatives of the proband were heterozygous carriers of the same variant, while no variations were detected in this gene of his father and other unaffected males. Based on the ACMG criteria, the novel c.216_217del variant of the TRAPPC2 gene was the pathogenic variant of this SEDT family. CONCLUSION:In this study we identified the novel pathogenic variant of of c.216_217del in the gene of TRAPPC2 in this five-generation Chinese SEDT family. Our findings expand the clinical and molecular spectrum of SEDT and helps the genetic diagnosis of SEDT patients.

Dataset Information

X-linked Spondyloepiphyseal Dysplasia Tarda with Mutation in TRAPPC2Gene: First Report from India.

Publications

X-linked Spondyloepiphyseal Dysplasia Tarda with Mutation in TRAPPC2Gene: First Report from India.

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